Proceedings of the 38th Annual ASTRO Meeting

49 IRRADIATION IN THE SETTING OF COLLAGEN VASCULAR DISEASE:

ACUTE AND LATE TOXICITY

183

Monica Morris, M.D., Simon Powell, M.D. Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

Purpose: Based upon reports of greater toxicity from radiation therapy, collagen vascular diseases have been considered a contraindication to irradiation. We assessed the acute and late complication rate of radiation therapy in patients with collagen vascular disease.

Methods & Materials: A retrospective chart review was undertaken to analyze acute and late toxicity in the 96 patients with documented collagen vascular disease (CVD) who were irradiated between 1960 and 1995. The majority had rheumatoid arthritis (55); 14 had systemic lupus erythematosus; 7 polymyositis or dermatomyositis; 7 ankylosing spondylitis; 4 scleroderma; 2 juvenile rheumatoid arthritis; and the remainder various mixed connective tissue disorders. Mean follow up of survivors was 6.3 years from time of irradiation. Treatment was megavoltage in all but 8 cases. Doses ranged from 6 to 70Gy, with an average of 41.7Gy. Treatment of 32 sites was combined with chemotherapy, 15 concurrent with irradiation. Surgery was involved in the treatment of 46 sites. Toxicity was scored using the RTOG acute and the RTOG/EORTC Late Effects on Normal Tissues radiation morbidity scoring scales.

Results: Overall, 127 sites were evaluable in 96 patients. Significant (grade 3 or higher) acute complications were seen in 15 of 127 (11.8%) of irradiated sites. The actuarial incidence of significant late complications at 5 and 10 years was 16% and 2446, respectively. There was a single in-field sarcoma. 2 patients had treatment- related deaths, one from leukencephalopathy and the other from postoperative wound infection. Univariate analysis revealed late effects to be more severe in those receiving combined modality treatment (p=.O3), and in those with significant acute reactions (p=.OOOl). Patients with rheumatoid arthritis had less severe late effects than those with other collagen vascular diseases (6% vs 37% at 5 years, p=.OOOl). We did not demonstrate a difference in late effects according to radiation dose, timing of CVD onset, or by clinical or serologic measures of disease activity.

Conclarion: An increased rate of late radiation toxicity was found in patients with CVD, as compared to the 5- 10% rate expected for a general population. The exception was in rheumatoid arthritis, which was not associated with increased toxicity. Caution should be exercised in the irradiation of those patients with non- rheumatoid CVD, particularly where combined modality therapy is planned.

50 PRKVENTIONOFHETEROTOPIC OSSIFICATIONABOIJTTHE HIP ~~~GPER~OPERAT~ERADIOTHERAPY:

RESULTSOFTWORANDOMIZEDTR~ALSIN~~OPATIENTS.

M. H&rich Seegenschmiedt”, MD; Ludwig Keiholz, MD; Peter Mart&, PhD; Rainer WSIfel’, MD; Friedrich Henning’, MD; Rolf Sauer”, MD ; (*) Department of Radiation Oncology, (’ ) Department of Surgery, (“) Institute of Medical Statistics & Documentation,

University of Erlangen-Niirnberg, Universita’tsstr 27, 91054 Erlangen ( Germany ); Hahnemann University, Philadelphia PA 19102 (USA)

BACKGROUND: In-viva data (Ku&x~~~h el al., 1991) indicate the efficacy of pre- and postoperative radiotherapy (RT) in suppressing development of heterotopic ossification (HO) after hip surgery Since 1987 two prospective randomized trials were initiated at our institution to assess the comparative eficacy of ,,high-dose RT‘ versus ,,low-dose RT’ (HOP study I) and ,,preoperative RT‘ versus ,,postoperative RT’ (HOP study 2). A control arm without radiotherapy (RT) was avoided, as only those patients (pts) were entered, who had a very high risk to develop HO atIer hip arthroplasty.

PATENTS & METHODS: In HOP study 1 (accrual: June 1987 - June 1992), 249 pts were randomized between the folloting~fqxrutiw RT .whddes: ,&-dose RT‘ with 5 x 2 Gy, IO Gy total RT dose (N = 129) versus ,,high dose Rr with 5 x 3.5 Gy, 17.5 Gy total RT dose (N = 121); RT was applied with daily fractionation starting at postoperative day I - 4. In HOP study 2 (accrual : July 1992 - July 1995), 161 pts were randomized between ,,preoperative RT’ using a single dose of 7 Gy (N = 80 pts) and postoperative RT with 5 x 3.5 Gy (N = 5 I pts). In both studies only patients were includes with one or multiple of the following risk factors for HO: ipsi- (55%) or contralateral HO (33%). hypertrophic osteoarthritis (48%), repeated hip surgery, acetabular fracture or severe hip trauma (43%); 62% of all pts had at least two risk factors. The structure of the relevant and possibly confounding patient and disease parameters and risk factors was similar in each of the treatment arms within the two randomized studies. - The assessment of “treatment failures” was based upon the comparison of the amount of HO seen on the immediately postoperative radiograph as compared to radiographs obtained at least 6 months after surgery (Brooker Score) Any progression of HO by Brooker score was regarded as treatment failure

RESULTS: At last FU, in January 1996 both studies 369 of410 pts (90%) had received an effective prophylaxis without increased HO at last FU, while 41 pts (IO%) had developed an increased HO postoperatively (“mdiol~~cal Irealnle,,lfailr,rrs”). In HOP study 1, 22 patients (9%) developed Brooker failures, i e 7 (6%) after receiving ,,high dose Rr and 15 (12%) tier ,,low dose RT“ (p = 0.12; ns). In HOP study 2, 19 patients (12%) developed Brooker failures, I5 (I 9%) after receiving ,.preoperative RT‘ and 4 (5%) after receiving ,,postoperative RT‘ (p < 0.01). However, in HOP study 2 only those patients were at a significantly higher risk to develop Brooker failures, which had a preoperative ipsilaterai HO Brooker grade 3 or 4 and received preoperative RT (I l/28 = 39% failures), while postoperative RT led to satisfactory results (2/22 = 8% failures). In multivariate analysis, the following parameters were found as prognostic factors : delayed RT initiation (later than day 4 postoperatively) (p = 0 0026), pattern of HO risk factors (p = 0.04) in HOP study I; sex (p = 0 02), preoperative Brooker grade (p = 0.001) and RT schedule (p = 0.01) in HOP study 2 The Harris score was not generally correlated with the Brooker score, but patients with Brooker Score grade 3 and 4 had a significantly worse functional hip status.

CONCLUSIONS: (a) Pre- and postoperative RT after hip ar,!?roplasty is a very effective prophylaxis to prevent HO even in high-risk patients without any compromise to the early implant fixation (b) The higher RT dose (17.5 Gy9 and the postoperative RT schedule yields slightly superior results than the lower RT dose (IO Gy) and preoperative RT (7 Gy) (c) Preoperative RT provides excellent outcome for low ipsilateral Brooker grades I and 2, while it is insufficient for high Brooker grades 3 and 4. (d) Further clinical and radiobiological research is warranted